Effect of glycemic control on electrophysiologic changes of diabetic neuropathy in type 2 diabetic patients

Diabetic neuropathy is a common complication of diabetes mellitus. Effective blood glucose control retards changes in nerve conduction velocity in type 1 diabetes. This study examined the relationship between glycemic control and electrophysiologic changes in diabetic neuropathy in 57 type 2 diabetic patients. Nerve conduction in the peroneal motor nerve, tibial motor nerve, and sural nerve were measured at study entry and at follow-up 24+/-3.12 months later. Changes in individual nerves are expressed as a percentage change (PC) and overall electrophysiologic changes are expressed as the sum of individual PCs. The PCs for peroneal motor nerve velocity, tibial motor nerve velocity, and sural nerve velocity were all lower in patients with a mean HbA1c of 8.5% or less compared with those in patients with a mean HbA1c of more than 8.5%, and SPCV (sum of PC in velocity) was significantly inversely correlated with mean HbA1c. However, there was no significant difference in SPCV in subjects with or without hypertension, hypertriglyceridemia, or low high-density lipoprotein cholesterol concentration. In conclusion, hyperglycemia is the most important etiology for electrophysiologic progression in type 2 diabetic patients. Furthermore, a mean HbA1c of more than 8.5% will result in significant deterioration in electrophysiology.     

Effects of insulin-sensitising agents in mice with hepatic insulin resistance

Aims/hypothesis The metabolic abnormalities of insulin resistance are ameliorated by insulin sensitisers via different mechanisms. Metformin decreases hepatic glucose output, whereas rosiglitazone (RSG) is an agonist for peroxisome proliferator activated receptor (PPAR), highly expressed in fat. To gain insight into the mechanisms of action of these drugs, we compared their actions in two models of insulin resistance: the obese, hyperglycaemic ob/ob mouse and the liver specific insulin receptor knockout (LIRKO) mouse.Methods Control, ob/ob, and LIRKO mice were divided into three groups that received metformin (300 mg/kg body weight/day), RSG (3 mg/kg body weight/day), or placebo for 3 weeks.Results In the presence of the severe hepatic insulin resistance of the LIRKO mouse, neither metformin nor RSG had any significant effect on glucose or insulin tolerance tests. On the other hand, RSG decreased serum concentrations of total cholesterol, LDL, and HDL in LIRKO mice. Adipocyte PPAR gene and protein expression, and adipocyte size were all increased in LIRKO mice treated with RSG, whereas fat-cell size in control animals was decreased by RSG.Conclusion/interpretation TZDs probably improve some lipid parameters of the dysmetabolic syndrome associated with diabetes mellitus even in the presence of absolute hepatic insulin resistance, but both metformin and TZDs require an operating insulin signalling system in the liver for their effects in glucose homeostasis.Abbreviations TZD Thiazolidinedione - RSG rosiglitazone - LIRKO liver specific insulin receptor knockout     

Prediction of human transplantation arteriopathy and coronary events with lung/heart count ratios during intravenous dipyridamole thallium-201 imaging

BACKGROUND: Cardiac allograft arteriopathy often limits long-term survival in transplantation recipients but has been difficult to detect by standard diagnostic methods. Because of the diffuse nature of transplantation coronary disease, we postulated that a lung/heart ratio during dipyridamole thallium imaging might better predict arteriopathy-related complications than diagnostic methods that detect discrete luminal stenoses. METHODS AND RESULTS: Sixty-six unselected heart transplantation recipients were evaluated with annual coronary arteriograms, endomyocardial biopsy, and intravenous dipyridamole thallium testing (initial study group). The mean lung/heart ratio on an anterior planar image was 0.40 for all patients; therefore <0.40 was arbitrarily defined as normal. After October 1992, 98 patients were tested (validation study group) and a lung/heart ratio cutoff of 0.40 was evaluated prospectively. Coronary end points were defined as (1) at least 1 coronary artery stenosis >/=50% of the luminal diameter, (2) sudden cardiac death, and (3) acute myocardial infarction. Stepwise logistic regression analysis was performed to identify independent predictors of future coronary end points. For the initial study group, the lung/heart ratio on the first annual thallium study was the only independent predictor of subsequent cardiac end points (0.47 +/- 0.13 [SD] with end points vs 0.38 +/- 0.11 without end points, P <.05). For the validation study group, independent predictors of subsequent coronary events included the lung/heart ratio and the radionuclide left ventricular ejection fraction. No patient with a lung/heart ratio <0.40 and a left ventricular ejection fraction >/=0.50 developed a cardiac event during 21 +/- 11 months of follow-up. CONCLUSIONS: A lung/heart ratio >/=0.40 on dipyridamole thallium testing is a sensitive predictor of coronary events after heart transplantation. Patients with heart transplantion who have a lung/heart ratio <0.40 and normal systolic left ventricular function are at low risk for subsequent coronary events and may not require annual surveillance by coronary arteriography.     

Activation of the myogenin promoter during mouse embryogenesis in the absence of positive autoregulation.

Myogenin, a member of the MyoD family of helix-loop-helix proteins, can induce myogenesis in a wide range of cell types. In addition to activating muscle structural genes, members of the MyoD family can autoactivate their own and cross-activate one another's expression in transfected cells. This has led to the hypothesis that autoregulatory loops among these factors provide a mechanism for amplifying and maintaining the muscle-specific gene expression program in vivo. Here, we make use of myogenin-null mice to directly test this hypothesis. To investigate whether the myogenin protein autoregulates the myogenin gene during embryogenesis, we introduced a myogenin-lacZ transgene into mice harboring a null mutation at the myogenin locus. Despite a severe deficiency of skeletal muscle in myogenin-null neonates, the myogenin-lacZ transgene was expressed normally in myogenic cells throughout embryogenesis. These results show that myogenin is not required for regulation of the myogenin gene and argue against the existence of a myogenin autoregulatory loop in the embryo.     

An expanded prevention quality diabetes composite: Quantifying the burden of preventable hospitalizations for older adults with diabetes

Aim

To expand the existing United States Agency for Health Research and Quality (AHRQ) Diabetes composite (AHRQ-DC) to include additional preventable hospitalizations specific or relevant to diabetes.

A 15-minute [13C]-urea breath test for the diagnosis of Helicobacter pylori infection in patients with non-ulcer dyspepsia

BACKGROUND: Non-ulcer dyspepsia (NUD) accounts for the majority of dyspeptic patients and studies on the epidemiology of Helicobacter pylori infection in NUD depend on a non-invasive and rapid diagnostic test. This study was performed to determine the sensitivity and specificity of a 15-min simplified protocol of the [13C]-urea breath test ([13C]-UBT) for the diagnosis of H. pylori infection in patients with NUD. METHODS: One hundred and thirty-six patients with a clinical and endoscopic diagnosis of NUD were included. The [13C]-UBT was modified from the European standard protocol. The baseline breath sample was collected 5 min after the patient took a test meal and the 13CO2 was collected 15 min after the patient drank 100 mg [13C]-urea. The gold standard used for comparison was either a positive culture or positive histology + positive rapid urease test sampled on upper gastrointestinal endoscopy. RESULTS: The prevalence of H. pylori infection in NUD by the gold standard was 59.6%, whereas that calculated by the [13C]-UBT was 60.3%. The sensitivity and specificity of [13C]-UBT was 93.8 and 89.1% compared with the gold standard. The shortened collection time and simplification of the procedure may have led to a decline in specificity. CONCLUSION: The 15-min [13C]-UBT is a rapid but less specific protocol for detecting the presence of H. pylori infection in patients with NUD.     

The inverse relationship between chronic HBV and HCV infections among injection drug users is associated with decades of age and drug use

Summary.  Infection with hepatitis C virus (HCV) may suppress co-infection with hepatitis B virus (HBV) during acute or chronic HBV infection. We examined relationships between HBV infection, HCV infection and other factors among injection drug users (IDUs) with antibodies to both viruses. Participants enrolled in a cross-sectional study during 1998–2000 were considered to have been infected with HBV if they had core antibody, to be chronically infected if they had hepatitis B surface antigen (HBsAg), to have been infected with HCV if they had HCV antibody and to be chronically infected if they had HCV RNA. Among 1694 participants with antibody to both viruses, HBsAg prevalence decreased with increasing age among those positive for HCV RNA [from 4.55% in those 18–29 years to 1.03% in those ≥50 years old ( P _trend = 0.02)], but not among those who were negative for HCV RNA. Chronic HBV infection was less common overall among those with chronic HCV infection (odds ratio [OR], 0.25; P  < 0.0001), but this inverse relationship was much stronger in the oldest (>50 years; OR = 0.15) than the youngest (18–29 years; OR = 0.81) participants ( P _trend = 0.03). Similar results were obtained when duration of injection drug use was substituted for age ( P _trend = 0.05). Among IDUs who have acquired both HBV and HCV, chronic HBV infection is much less common among those with chronic HCV infection, but this inverse relationship increases markedly with increasing years of age and injection drug use. Co-infection with HCV may enhance the resolution of HBsAg during the chronic phases of these infections.